In-vitro metabolic inhibition and antifertility effect facilitated by membrane alteration: search for novel antifertility agent using nifedipine analogues

Eur J Med Chem. 2011 Sep;46(9):3581-9. doi: 10.1016/j.ejmech.2011.05.022. Epub 2011 May 19.

Abstract

In search of non-hormonal male contraceptives, analogues of nifedipine, which causes reversible infertility, have been synthesized and their interaction at molecular level with model membrane has been probed. Analogues act differently with respect to their antifertility action. This is achieved by altering the cell metabolism thereby directly affecting the motility which is responsible for fertility. Secondly, these drugs bind differently to the interior of the cell-membrane affecting the membrane fluidity, architecture and dynamics. Sulfasalazine and D(4) interact to a larger extent and alter the lipid bilayer phase to a hexagonal. D(1), D(2) and D(3) do not have considerable effect. D(4) is the most promising candidate as a lead compound for the development of novel non-hormonal male antifertility agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calorimetry, Differential Scanning
  • Cell Membrane / drug effects
  • Contraceptive Agents, Male / pharmacology*
  • Humans
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Male
  • Nifedipine / analogs & derivatives*
  • Nifedipine / pharmacology
  • Sperm Motility / drug effects

Substances

  • Contraceptive Agents, Male
  • Nifedipine